The present invention relates to improvements in and relating to magnetic resonance imaging (MRI) and in particular to apparatus for and methods of electron spin resonance enhanced magnetic resonance imaging (ESREMRI).
ESREMRI, described by us in EP-A-296833 (Leunbach), is a method of magnetic resonance imaging in which amplification of the nuclear magnetic resonance signal, the free induction decay (FID) signal, is achieved by stimulating an electron spin resonance transition of a paramagnetic species present in the subject being imaged. Stimulation of the ESR transition leads to a polarization of the nuclear spin system responsible for the FID signals from which the magnetic resonance (MR) image of the subject is generated. This so called dynamic nuclear polarization is in effect an overpopulation, relative to equilibrium values, of the excited nuclear spin state and can be so large that the FID signal may be amplified by a factor of well over 100.
Using this technique, MR images may be generated by conventional imaging procedures, such as for example two and three dimensional Fourier transform, with enhanced signal to noise (SN) ratios (due to the amplification of the FID signal) and/or with shorter image acquisition times (since the nuclear spin system does not have to be allowed to relax towards equilibrium over a period comparable with T.sub.1, the spin-lattice relaxation time, for example about 1 second, between each excitation /FID signal detection cycle) and/or at lower strength primary magnetic fields than are conventionally utilized in MRI, e.g. 0.002 to 0.1 T or lower.
ESREMRI involves exposing the subject being imaged to pulses of electromagnetic radiation of frequencies selected such that ESR and NMR transitions are stimulated.
These frequencies are of course dependent on the strength of the primary magnetic field of the imaging apparatus; however, since, at the field strengths conventionally used in MRI, the ESR and NMR stimulating radiations are generally microwave (MW) and radiofrequency (RF) radiations, for the sake of convenience the ESR and NMR stimulating radiations will be referred to hereinafter as being MW and RF radiations respectively.
To maximize the FID signal enhancement in ESREMRI, the ESR transition(s) of the paramagnetic species, which may be naturally present in the subject being imaged but more generally will be administered to the subject as a contrast agent, should be stimulated at or near saturation level for a period leading up to the initial RF pulse of the RF pulse/FID signal detection cycle of the MR image acquisition procedure.
Exposure of live subjects to electromagnetic radiation of RF or MW frequencies (including the radiations of lower frequencies than are conventionally considered to be MW or RF but which are encompassed herein by those terms by virtue of the definition given above) may cause undesirable heating of the subject's tissues to occur and clearly it is essential for a diagnostic technique such as MRI (and ESREMRI) that the temperature increases in the tissue be kept down to an acceptable level.
To avoid excessive RF heating, there are recommendations for conventional MRI that the maximum radiation exposure, the specific absorption rate (SAR), should be about 1-8 W/kg bodyweight during the imaging procedure. If MRI is conducted in accordance with these recommendations, any tissue temperature rises should be acceptably low, e.g. less than about 1.degree. C., even for extended imaging periods.
Irradiation at power levels well above those recommended values however can be tolerated as long as the pulse duration of such radiation is short. Indeed, where pulsed RF or MW radiation is applied its heating effect may be lower than that of continuous wave radiation even where the SAR averaged over the whole exposure period may be much higher. Thus, some MR imagers operate using pulsed RF radiation where the SAR calculated for each pulse far exceeds the recommended maximum but where the SAR averaged over the exposure period is below that maximum.
As mentioned above, ESREMRI involves exposing the subject being imaged not just to the nuclear magnetic resonance stimulating RF radiation that is conventional within MRI, but also to electron spin resonance stimulating MW radiation. Accordingly, it is particularly important in in vivo ESREMRI to avoid undue exposure of the subject to MW radiation whereby to avoid undue heating of the subject's tissues.
In order that MW exposure be kept to an acceptable level we suggested in EP-A-296833 that any paramagnetic contrast agent used as the source of the MW stimulated ESR transitions should have an ESR spectrum in which the stimulated transition(s) should have a linewidth of less than 1 gauss. This effectively excluded from consideration the paramagnetic metal compounds, e.g. chelates, salts, etc., that have been found in conventional MRI to be effective T.sub.1 contrast agents. Instead EP-A-296833 focused attention on the suitability as ESREMRI contrast agents of various stable free radicals, such as for example nitroxides. However, those nitroxide stable free radicals which have ESR linewidths of less than 1 gauss generally are less efficient as T.sub.1 contrast agents in MRI--more specifically they generally have lower relaxivities or specific relaxation rate (1/T.sub.1) enhancement values than do the paramagnetic metal species--containing T.sub.1 contrast agents. Accordingly, up to now, choice of ESREMRI as an imaging technique has meant that a relatively low relaxivity contrast agent had to be used and that contrast agent dosages have had to be relatively high.
We have now found that MW exposure may be reduced or maintained within acceptable levels and that the choice of suitable contrast agents may be expanded by performing ESREMRI using the Echo Planar Imaging (EPI) technique developed by Mansfield for conventional MRI (see Mansfield P, J.Phys.C.10:L55-58 (1977)). The new technique according to the invention moreover represents an improvement in the performance of EPI since ESREMRI may be performed using primary magnetic fields lower in field strength than those primary fields generally used in MRI and may thus benefit from all the advantages of operating at lower primary field strengths.
Thus, whereas in MRI techniques such as back projection and two- and three-dimensional Fourier transform generation of a single image requires many RF excitation/FID signal detection cycles, in EPI a single RF excitation/FID signal detection cycle may be all that is required. This is made possible by echo regeneration of FID signals by rapid and repeated switching of the polarity of the read gradient. As a result of this rapid switching, the magnetic field variation (dG/dt) experienced by the subject being imaged can be high. Rapid magnetic field changes are considered undesirable for live subjects, but by operating at the low primary field strengths of for example 500 gauss or below, especially 200 gauss or below, that are utilizable for ESREMRI, smaller magnitude magnetic field gradients than are conventional in MRI may be used and as a result the magnetic field variation dG/dt in EPI may be reduced, or the FID signal utilization may be enhanced by switching the gradient polarity more rapidly.